Trial Outcomes & Findings for Impact of EMpagliflozin on Cardiac Function and Biomarkers of Heart Failure in Patients With Acute MYocardial Infarction (NCT NCT03087773)

Last Updated: 2024-08-22

Results Overview

Difference in the change of nt-proBNP (N terminales pro brain natriuretic peptide) levels between treatment groups from randomization to week 26

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

476 participants

Primary outcome timeframe

26 weeks

Results posted on

2024-08-22

Participant Flow

Recruitment between May 2017 (FPFV) and Oct 2021 (LPFV), at 11 sites: 1) University Hospital Graz; 2) Hospital Klagenfurt 3) Brothers of Saint John of God Eisenstadt; 4) Paracelsus Medical Private University Salzburg; 5) Vorarlberg Institute for Vascular Investigation and Treatment; 6) Kardinal Schwarzenberg Hospital Schwarzach; 7) J. Kepler University Hospital Linz; 8) University Hospital St. Pölten; 9) Allgemeines Krankenhaus Vienna; 10) Hospital Graz II: 11) Hospital Landstrasse Vienna

Participant milestones

Participant milestones
Measure	Empagliflozin The subjects will receive Empagliflozin 10mg. Empagliflozin 10 mg: The subject will receive Empagliflozin 10 mg orally once daily for 26 weeks.	Placebo Oral Tablet The subjects will receive placebo. Placebo Oral Tablet: The subject will receive Placebo orally once daily for 26 weeks.
Overall Study STARTED	237	239
Overall Study COMPLETED	217	227
Overall Study NOT COMPLETED	20	12

Reasons for withdrawal

Reasons for withdrawal
Measure	Empagliflozin The subjects will receive Empagliflozin 10mg. Empagliflozin 10 mg: The subject will receive Empagliflozin 10 mg orally once daily for 26 weeks.	Placebo Oral Tablet The subjects will receive placebo. Placebo Oral Tablet: The subject will receive Placebo orally once daily for 26 weeks.
Overall Study Withdrawal by Subject	8	4
Overall Study Lost to Follow-up	12	8

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Empagliflozin n=237 Participants The subjects will receive Empagliflozin 10mg. Empagliflozin 10 mg: The subject will receive Empagliflozin 10 mg orally once daily for 26 weeks.	Placebo Oral Tablet n=239 Participants The subjects will receive placebo. Placebo Oral Tablet: The subject will receive Placebo orally once daily for 26 weeks.	Total n=476 Participants Total of all reporting groups
Age, Continuous	57 years n=237 Participants	57 years n=239 Participants	57 years n=476 Participants
Sex: Female, Male Female	42 Participants n=237 Participants	42 Participants n=239 Participants	84 Participants n=476 Participants
Sex: Female, Male Male	195 Participants n=237 Participants	197 Participants n=239 Participants	392 Participants n=476 Participants
Race and Ethnicity Not Collected	—	—	0 Participants Race and Ethnicity were not collected from any participant.
Region of Enrollment Austria	237 Participants n=237 Participants	239 Participants n=239 Participants	476 Participants n=476 Participants
Body Mass Index	27.7 kg/m² n=237 Participants	27.2 kg/m² n=239 Participants	27.6 kg/m² n=476 Participants
Systolic blood pressure	125 mmHg n=237 Participants	125 mmHg n=239 Participants	125 mmHg n=476 Participants
Diastolic blood pressure	78 mmHg n=237 Participants	78 mmHg n=239 Participants	78 mmHg n=476 Participants
Obesity	68 Participants n=237 Participants	70 Participants n=239 Participants	138 Participants n=476 Participants
Type 2 diabetes	30 Participants n=237 Participants	33 Participants n=239 Participants	63 Participants n=476 Participants
Hypertension	92 Participants n=237 Participants	107 Participants n=239 Participants	199 Participants n=476 Participants
Dyslipidaemia	71 Participants n=237 Participants	64 Participants n=239 Participants	135 Participants n=476 Participants
Smoking active or former	171 Participants n=237 Participants	170 Participants n=239 Participants	341 Participants n=476 Participants
Coronary artery disease	28 Participants n=237 Participants	25 Participants n=239 Participants	53 Participants n=476 Participants
History of stroke	5 Participants n=237 Participants	1 Participants n=239 Participants	6 Participants n=476 Participants
History of coronary artery bypass graft	1 Participants n=237 Participants	1 Participants n=239 Participants	2 Participants n=476 Participants
History of myocardial infarction	14 Participants n=237 Participants	9 Participants n=239 Participants	23 Participants n=476 Participants
Depression	15 Participants n=237 Participants	9 Participants n=239 Participants	24 Participants n=476 Participants
History of carcinoma	11 Participants n=237 Participants	13 Participants n=239 Participants	24 Participants n=476 Participants
Coronary 3-vessel disease	50 Participants n=237 Participants	36 Participants n=239 Participants	86 Participants n=476 Participants
Coronary 2-vessel disease	82 Participants n=237 Participants	80 Participants n=239 Participants	162 Participants n=476 Participants
Coronary 1-vessel disease	105 Participants n=237 Participants	123 Participants n=239 Participants	228 Participants n=476 Participants
Angiotensin-converting enzyme inhibitor/angiotensin receptor blocker	96 Participants n=237 Participants	97 Participants n=239 Participants	193 Participants n=476 Participants
Angiotensin receptor-neprilysin inhibitor	2 Participants n=237 Participants	7 Participants n=239 Participants	9 Participants n=476 Participants
Beta-blocker	223 Participants n=237 Participants	234 Participants n=239 Participants	457 Participants n=476 Participants
Mineralcorticoid receptor antagonist	86 Participants n=237 Participants	94 Participants n=239 Participants	180 Participants n=476 Participants
Loop diuretic	27 Participants n=237 Participants	24 Participants n=239 Participants	51 Participants n=476 Participants
Statin	229 Participants n=237 Participants	233 Participants n=239 Participants	462 Participants n=476 Participants
Ezetimibe	29 Participants n=237 Participants	30 Participants n=239 Participants	59 Participants n=476 Participants
Calcium channel blocker	9 Participants n=237 Participants	12 Participants n=239 Participants	21 Participants n=476 Participants
Aspirin	235 Participants n=237 Participants	239 Participants n=239 Participants	474 Participants n=476 Participants
Anticoagulatoin drugs	16 Participants n=237 Participants	21 Participants n=239 Participants	37 Participants n=476 Participants
Metformin	21 Participants n=237 Participants	20 Participants n=239 Participants	41 Participants n=476 Participants
Dipeptidyl peptidase 4 inhibitor	7 Participants n=237 Participants	6 Participants n=239 Participants	13 Participants n=476 Participants
Sulfonylurea	2 Participants n=237 Participants	2 Participants n=239 Participants	4 Participants n=476 Participants
Glucagon-like peptide-1 receptor agonist	2 Participants n=237 Participants	2 Participants n=239 Participants	4 Participants n=476 Participants
Insulin	5 Participants n=237 Participants	6 Participants n=239 Participants	11 Participants n=476 Participants
N-terminal prohormone of brain natriuretic peptide	1,272 pg/mL n=237 Participants	1,373 pg/mL n=239 Participants	1,294 pg/mL n=476 Participants
Estimated glomerular filtration rate	92 ml/min/1.73m² n=237 Participants	91 ml/min/1.73m² n=239 Participants	92 ml/min/1.73m² n=476 Participants
HbA1c	5.6 percentage of HbA1c n=237 Participants	5.7 percentage of HbA1c n=239 Participants	5.6 percentage of HbA1c n=476 Participants
Creatine kinase	1,668 U/L n=237 Participants	1,701 U/L n=239 Participants	1,673 U/L n=476 Participants
Troponin T	3,059 ng/L n=237 Participants	3,029 ng/L n=239 Participants	3,039 ng/L n=476 Participants
Total cholesterol	188 mg/dL n=237 Participants	188 mg/dL n=239 Participants	188 mg/dL n=476 Participants
Low-density lipoprotein	118 mg/dL n=237 Participants	121 mg/dL n=239 Participants	120 mg/dL n=476 Participants
High-density lipoprotein	44 mg/dL n=237 Participants	43 mg/dL n=239 Participants	44 mg/dL n=476 Participants
Aspartate aminotransferase	203 U/L n=237 Participants	212 U/L n=239 Participants	204 U/L n=476 Participants
Alanine aminotransferase	50 U/L n=237 Participants	50 U/L n=239 Participants	50 U/L n=476 Participants
Gamma glutamyltransferase	29 U/L n=237 Participants	32 U/L n=239 Participants	31 U/L n=476 Participants

PRIMARY outcome

Timeframe: 26 weeks

Difference in the change of nt-proBNP (N terminales pro brain natriuretic peptide) levels between treatment groups from randomization to week 26

Outcome measures

Outcome measures
Measure	Empagliflozin n=217 Participants The subjects will receive Empagliflozin 10mg. Empagliflozin 10 mg: The subject will receive Empagliflozin 10 mg orally once daily for 26 weeks.	Placebo Oral Tablet n=227 Participants The subjects will receive placebo. Placebo Oral Tablet: The subject will receive Placebo orally once daily for 26 weeks.
Changes of Nt-proBNP (N-terminales Pro Brain Natriuretic Peptide) Levels	-84.9 pg/mL Interval -91.7 to -72.6	-82.2 pg/mL Interval -89.2 to -69.8

SECONDARY outcome

Timeframe: 26 weeks

Population: Total ultrasound measurements were just available from 212 (empagliflozin group) and 209 patients (placebo group).

Difference in the change of ejection fraction between treatment groups from randomization to week 26 Ejection fraction was measured by ultrasound.

Outcome measures

Outcome measures
Measure	Empagliflozin n=212 Participants The subjects will receive Empagliflozin 10mg. Empagliflozin 10 mg: The subject will receive Empagliflozin 10 mg orally once daily for 26 weeks.	Placebo Oral Tablet n=209 Participants The subjects will receive placebo. Placebo Oral Tablet: The subject will receive Placebo orally once daily for 26 weeks.
Changes in Ejection Fraction	4.7 percentage of ejection fraction Interval 3.6 to 5.8	2.8 percentage of ejection fraction Interval 1.8 to 3.9

SECONDARY outcome

Timeframe: 26 weeks

Population: Total ultrasound measurements were just available from 212 (empagliflozin group) and 209 patients (placebo group).

Difference in the change of left ventricular end-diastolic volume from randomization to week 26 (measured by ultrasound)

Outcome measures

Outcome measures
Measure	Empagliflozin n=212 Participants The subjects will receive Empagliflozin 10mg. Empagliflozin 10 mg: The subject will receive Empagliflozin 10 mg orally once daily for 26 weeks.	Placebo Oral Tablet n=209 Participants The subjects will receive placebo. Placebo Oral Tablet: The subject will receive Placebo orally once daily for 26 weeks.
Changes in Left Ventricular End-diastolic Volume	3.4 ml Interval -0.7 to 7.4	13.5 ml Interval 8.7 to 18.3

SECONDARY outcome

Timeframe: 30 weeks

Difference in the duration of hospital stay between the treatment groups after initiation of the study treatment. This outcome measure includes all days of an inpatient stay in a hospital after the initial discharge.

Outcome measures

Outcome measures
Measure	Empagliflozin n=217 Participants The subjects will receive Empagliflozin 10mg. Empagliflozin 10 mg: The subject will receive Empagliflozin 10 mg orally once daily for 26 weeks.	Placebo Oral Tablet n=227 Participants The subjects will receive placebo. Placebo Oral Tablet: The subject will receive Placebo orally once daily for 26 weeks.
Duration of Hospital Stay	6.0 days Interval 3.0 to 9.0	6.0 days Interval 3.0 to 9.0

SECONDARY outcome

Timeframe: From Baseline to Week 26

Population: Total ultrasound measurements were just available from 212 (empagliflozin group) and 209 patients (placebo group).

E/E' ratio is a measure of left ventricular filling pressure. The E/e' ratio is a parameter for diastolic function assessment that is frequently used for Heart failure with preserved ejection fraction evaluation. To derive the E/e´ ratio one must divide the maximum velocity of the E-wave of mitral valve inflow by the maximal velocity of E. In normal individuals the E/e´ ratio is \<8. In the presence of diastolic dysfunction / impaired relaxation, e´ will be rather low. In contrast, the E-wave increases with elevated filling pressures. Thus the E/e´ ratio will increase in the presence of diastolic dysfunction. An E/e´ratio \>14 is highly suggestive of elevated filling pressures.

Outcome measures

Outcome measures
Measure	Empagliflozin n=212 Participants The subjects will receive Empagliflozin 10mg. Empagliflozin 10 mg: The subject will receive Empagliflozin 10 mg orally once daily for 26 weeks.	Placebo Oral Tablet n=209 Participants The subjects will receive placebo. Placebo Oral Tablet: The subject will receive Placebo orally once daily for 26 weeks.
Changes in E/è Ratio From Baseline to Week 26	-9.7 Ratio Interval -13.1 to -6.4	-0.7 Ratio Interval -1.1 to -0.4

SECONDARY outcome

Timeframe: Baseline to Week 26

Population: Total ultrasound measurements were just available from 212 (empagliflozin group) and 209 patients (placebo group).

End-systolic volume (ESV) is the volume of blood in a ventricle at the end of contraction, or systole, and the beginning of filling, or diastole. Left ventricular end-systolic volume (LVESV) was measured at baseline and after 26 weeks by echocardiography.

Outcome measures

Outcome measures
Measure	Empagliflozin n=212 Participants The subjects will receive Empagliflozin 10mg. Empagliflozin 10 mg: The subject will receive Empagliflozin 10 mg orally once daily for 26 weeks.	Placebo Oral Tablet n=209 Participants The subjects will receive placebo. Placebo Oral Tablet: The subject will receive Placebo orally once daily for 26 weeks.
Changes in Left Ventricular End-systolic Volume (LVESV) From Baselin to Week 26	-3.6 ml Interval -6.3 to -1.0	4.3 ml Interval 1.2 to 7.4

Adverse Events

Empagliflozin

Serious events: 31 serious events

Other events: 18 other events

Deaths: 3 deaths

Placebo Oral Tablet

Serious events: 32 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Empagliflozin n=237 participants at risk The subjects will receive Empagliflozin 10mg. Empagliflozin 10 mg: The subject will receive Empagliflozin 10 mg orally once daily for 26 weeks.	Placebo Oral Tablet n=239 participants at risk The subjects will receive placebo. Placebo Oral Tablet: The subject will receive Placebo orally once daily for 26 weeks.
Cardiac disorders Any hospitalisation	13.1% 31/237 • Number of events 35 • Adverse events were collected from baseline to visit 5 (4 weeks after the end of intervention) - in total for 30 weeks. Adverse events (AE) that occured during this study were recorded on AE case report forms. The Sponsor reported all serious AEs (SAEs) and AEs which were relevant for a reported SAE as well as Adverse Events of Special Interest by fax using Böhringer Ingelheim (BI) SAE form to the BI Unique Entry Point. The sponsor reported the SAEs to the ethics committee and the local authorities as well as Boehringer Ingelheim Pharmacovigilance in accordance with the reporting instructions.	13.4% 32/239 • Number of events 34 • Adverse events were collected from baseline to visit 5 (4 weeks after the end of intervention) - in total for 30 weeks. Adverse events (AE) that occured during this study were recorded on AE case report forms. The Sponsor reported all serious AEs (SAEs) and AEs which were relevant for a reported SAE as well as Adverse Events of Special Interest by fax using Böhringer Ingelheim (BI) SAE form to the BI Unique Entry Point. The sponsor reported the SAEs to the ethics committee and the local authorities as well as Boehringer Ingelheim Pharmacovigilance in accordance with the reporting instructions.
Cardiac disorders Hospitalisation due to heart failure	1.3% 3/237 • Number of events 6 • Adverse events were collected from baseline to visit 5 (4 weeks after the end of intervention) - in total for 30 weeks. Adverse events (AE) that occured during this study were recorded on AE case report forms. The Sponsor reported all serious AEs (SAEs) and AEs which were relevant for a reported SAE as well as Adverse Events of Special Interest by fax using Böhringer Ingelheim (BI) SAE form to the BI Unique Entry Point. The sponsor reported the SAEs to the ethics committee and the local authorities as well as Boehringer Ingelheim Pharmacovigilance in accordance with the reporting instructions.	1.7% 4/239 • Number of events 4 • Adverse events were collected from baseline to visit 5 (4 weeks after the end of intervention) - in total for 30 weeks. Adverse events (AE) that occured during this study were recorded on AE case report forms. The Sponsor reported all serious AEs (SAEs) and AEs which were relevant for a reported SAE as well as Adverse Events of Special Interest by fax using Böhringer Ingelheim (BI) SAE form to the BI Unique Entry Point. The sponsor reported the SAEs to the ethics committee and the local authorities as well as Boehringer Ingelheim Pharmacovigilance in accordance with the reporting instructions.
Cardiac disorders Hospitalisation due to cardiovascular event	0.84% 2/237 • Number of events 2 • Adverse events were collected from baseline to visit 5 (4 weeks after the end of intervention) - in total for 30 weeks. Adverse events (AE) that occured during this study were recorded on AE case report forms. The Sponsor reported all serious AEs (SAEs) and AEs which were relevant for a reported SAE as well as Adverse Events of Special Interest by fax using Böhringer Ingelheim (BI) SAE form to the BI Unique Entry Point. The sponsor reported the SAEs to the ethics committee and the local authorities as well as Boehringer Ingelheim Pharmacovigilance in accordance with the reporting instructions.	2.1% 5/239 • Number of events 5 • Adverse events were collected from baseline to visit 5 (4 weeks after the end of intervention) - in total for 30 weeks. Adverse events (AE) that occured during this study were recorded on AE case report forms. The Sponsor reported all serious AEs (SAEs) and AEs which were relevant for a reported SAE as well as Adverse Events of Special Interest by fax using Böhringer Ingelheim (BI) SAE form to the BI Unique Entry Point. The sponsor reported the SAEs to the ethics committee and the local authorities as well as Boehringer Ingelheim Pharmacovigilance in accordance with the reporting instructions.

Other adverse events

Other adverse events
Measure	Empagliflozin n=237 participants at risk The subjects will receive Empagliflozin 10mg. Empagliflozin 10 mg: The subject will receive Empagliflozin 10 mg orally once daily for 26 weeks.	Placebo Oral Tablet n=239 participants at risk The subjects will receive placebo. Placebo Oral Tablet: The subject will receive Placebo orally once daily for 26 weeks.
Infections and infestations Urinary tract infection	4.6% 11/237 • Number of events 18 • Adverse events were collected from baseline to visit 5 (4 weeks after the end of intervention) - in total for 30 weeks. Adverse events (AE) that occured during this study were recorded on AE case report forms. The Sponsor reported all serious AEs (SAEs) and AEs which were relevant for a reported SAE as well as Adverse Events of Special Interest by fax using Böhringer Ingelheim (BI) SAE form to the BI Unique Entry Point. The sponsor reported the SAEs to the ethics committee and the local authorities as well as Boehringer Ingelheim Pharmacovigilance in accordance with the reporting instructions.	2.9% 7/239 • Number of events 8 • Adverse events were collected from baseline to visit 5 (4 weeks after the end of intervention) - in total for 30 weeks. Adverse events (AE) that occured during this study were recorded on AE case report forms. The Sponsor reported all serious AEs (SAEs) and AEs which were relevant for a reported SAE as well as Adverse Events of Special Interest by fax using Böhringer Ingelheim (BI) SAE form to the BI Unique Entry Point. The sponsor reported the SAEs to the ethics committee and the local authorities as well as Boehringer Ingelheim Pharmacovigilance in accordance with the reporting instructions.
Infections and infestations Genital fungal infection	3.0% 7/237 • Number of events 7 • Adverse events were collected from baseline to visit 5 (4 weeks after the end of intervention) - in total for 30 weeks. Adverse events (AE) that occured during this study were recorded on AE case report forms. The Sponsor reported all serious AEs (SAEs) and AEs which were relevant for a reported SAE as well as Adverse Events of Special Interest by fax using Böhringer Ingelheim (BI) SAE form to the BI Unique Entry Point. The sponsor reported the SAEs to the ethics committee and the local authorities as well as Boehringer Ingelheim Pharmacovigilance in accordance with the reporting instructions.	0.84% 2/239 • Number of events 2 • Adverse events were collected from baseline to visit 5 (4 weeks after the end of intervention) - in total for 30 weeks. Adverse events (AE) that occured during this study were recorded on AE case report forms. The Sponsor reported all serious AEs (SAEs) and AEs which were relevant for a reported SAE as well as Adverse Events of Special Interest by fax using Böhringer Ingelheim (BI) SAE form to the BI Unique Entry Point. The sponsor reported the SAEs to the ethics committee and the local authorities as well as Boehringer Ingelheim Pharmacovigilance in accordance with the reporting instructions.

Additional Information

Univ.-Prof. PD Harald Sourij, MD, MBA

Medical University of Graz

Phone: +43 316 385 81310

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place